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Canadian Brand Names

Use

Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as monotherapy when hyperglycemia cannot be managed on diet alone. May be used concomitantly with a sulfonylurea or insulin to improve glycemic control.

Warnings/Precautions

Lactic acidosis is a rare, but potentially severe consequence of therapy with metformin. Lactic acidosis should be suspected in any diabetic patient receiving metformin who has evidence of acidosis when evidence of ketoacidosis is lacking. Discontinue metformin in clinical situations predisposing to hypoxemia, including conditions such as cardiovascular collapse, respiratory failure, acute myocardial infarction, acute congestive heart failure, and septicemia.

Metformin is substantially excreted by the kidney. The risk of accumulation and lactic acidosis increases with the degree of impairment of renal function. Patients with renal function below the limit of normal for their age should not receive metformin. In elderly patients, renal function should be monitored regularly; should not be used in any patient

80 years of age unless measurement of creatinine clearance verifies normal renal function. Use of concomitant medications that may affect renal function (ie, affect tubular secretion) may also affect metformin disposition. Metformin should be suspended in patients with dehydration and/or prerenal azotemia. Therapy should be suspended for any surgical procedures (resume only after normal intake resumed and normal renal function is verified). Metformin should also be temporarily discontinued for 48 hours in patients undergoing radiologic studies involving the intravascular administration of iodinated contrast materials (potential for acute alteration in renal function).

Avoid use in patients with impaired liver function. Patient must be instructed to avoid excessive acute or chronic ethanol use. Administration of oral antidiabetic drugs has been reported to be associated with increased cardiovascular mortality; metformin does not appear to share this risk. Safety and efficacy of metformin have been established for use in children

10 years of age; the extended release preparation is for use in patients

Overdosage/Toxicology

Hypoglycemia (10% of cases) or lactic acidosis (~32% of cases) may occur. Metformin is dialyzable with a clearance of up to 170 mL/minute. Hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdose is suspected. Treatment is supportive.

Cationic drugs (eg, amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) which are eliminated by renal tubular secretion could have the potential for interaction with metformin by competing for common renal tubular transport systems

Children 10-16 years: Management of type 2 diabetes mellitus: Oral (500 mg tablet or oral solution): Initial: 500 mg twice daily (given with the morning and evening meals); increases in daily dosage should be made in increments of 500 mg at weekly intervals, given in divided doses, up to a maximum of 2000 mg/day

Doses of up to 2000 mg/day may be given twice daily. If a dose > 2000 mg/day is required, it may be better tolerated in three divided doses. Maximum recommended dose 2550 mg/day.

Extended release tablet: Initial: 500 mg once daily (with the evening meal); dosage may be increased by 500 mg weekly; maximum dose: 2000 mg once daily. If glycemic control is not achieved at maximum dose, may divide dose to 1000 mg twice daily. If doses >2000 mg/day are needed, switch to regular release tablets and titrate to maximum dose of 2550 mg/day.

Elderly: The initial and maintenance dosing should be conservative, due to the potential for decreased renal function. Generally, elderly patients should not be titrated to the maximum dose of metformin. Do not use in patients

80 years of age unless normal renal function has been established.

Transfer from other antidiabetic agents: No transition period is generally necessary except when transferring from chlorpropamide. When transferring from chlorpropamide, care should be exercised during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.

Concomitant metformin and oral sulfonylurea therapy: If patients have not responded to 4 weeks of the maximum dose of metformin monotherapy, consider a gradual addition of an oral sulfonylurea, even if prior primary or secondary failure to a sulfonylurea has occurred. Continue metformin at the maximum dose.

Failed sulfonylurea therapy: Patients with prior failure on glyburide may be treated by gradual addition of metformin. Initiate with glyburide 20 mg and metformin 500 mg daily. Metformin dosage may be increased by 500 mg/day at weekly intervals, up to a maximum of 2500 mg/day (dosage of glyburide maintained at 20 mg/day).

Decrease insulin dose 10% to 25% when FPG <120 mg/dL; monitor and make further adjustments as needed

Dosing adjustment/comments in renal impairment: The plasma and blood half-life of metformin is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance. Per the manufacturer, metformin is contraindicated in the presence of renal dysfunction defined as a serum creatinine >1.5 mg/dL in males, or >1.4 mg/dL in females and in patients with abnormal clearance. Clinically, it has been recommended that metformin be avoided in patients with Clcr<60-70 mL/minute (DeFronzo, 1999).

Dosing adjustment in hepatic impairment: Avoid metformin; liver disease is a risk factor for the development of lactic acidosis during metformin therapy.

Reference Range

Dietary Considerations

Drug may cause GI upset; take with food (to decrease GI upset). Take at the same time each day. Dietary modification based on ADA recommendations is a part of therapy. Monitor for signs and symptoms of vitamin B12 and/or folic acid deficiency; supplementation may be required.

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as directed (may take with food to decrease GI upset). Do not chew or crush tablets. Parts of extended-release tablets may be excreted in the stool (normal). Do not change dosage or discontinue without consulting prescriber. Avoid overuse of alcohol (could cause severe reaction). It is important to follow dietary and lifestyle recommendations of prescriber. You will be instructed in signs of hypo- or hyperglycemia by prescriber or diabetic educator. May cause drowsiness or dizziness (use caution driving or engaging in potentially hazardous tasks until response to drug is known); nausea or vomiting (taking with meals, eating small, frequent meals, frequent mouth care, or sucking lozenges may help); or abdominal distention, flatulence, diarrhea, constipation, or heartburn (if these persist consult prescriber for approved medication). Report immediately unusual weakness or fatigue; unusual muscle pain; persistent GI discomfort; dizziness or lightheadedness; sudden respiratory difficulty, chest discomfort, slow or irregular heartbeat; or other adverse reactions. Breast-feeding precaution: Breast-feeding is not recommended.

Anesthesia and Critical Care Concerns/Other Considerations

While megaloblastic anemia has been rarely seen with metformin, if suspected, vitamin B12 deficiency should be excluded. Metformin has a large volume of distribution in liver, kidney, and GI tract where concentration is much larger than in the plasma.

Lactic acidosis is an uncommon side effect in patients without renal or respiratory insufficiency, hepatic failure, or conditions that predispose to hypoxemia. Metformin should be avoided in diabetic patients with heart failure.

Cardiovascular Considerations

Metformin, alone or in combination with other agents (sulfonylurea), is effective in the management of diabetes. Lactic acidosis is an uncommon side effect in patients without renal or respiratory insufficiency, hepatic failure, or conditions that predispose to hypoxemia. As heart failure may affect renal and pulmonary function, metformin should be avoided or used with caution in diabetic patients with heart failure.